Association of CTLA-4 gene A/G polymorphism in Japanese type 1 diabetic patients with younger age of onset and autoimmune thyroid disease.

Abstract

Abbreviations: AITD, autoimmune thyroid disease; PCR, polymerase chain reaction; TG, thyroglobulin; TPO, thyroid peroxidase.A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances. Association of CTLA-4 Gene A/G Polymorphism in Japanese Type 1 Diabetic Patients With Younger Age of Onset and Autoimmune Thyroid Disease O R I G I N A L A R T I C L EOBJECTIVE -We studied the association between type 1 diabetes with autoimmune thyroid disease (AITD) and A/G allele polymorphism in exon 1 of the CTLA-4 gene in a Japanese population.RESEARCH DESIGN AND METHODS -We studied 74 Japanese type 1 diabetic patients with or without AITD and 107 normal subjects to identify the association between CTLA-4 polymorphism and type 1 diabetes using polymerase chain reaction-restriction fragment length polymorphism analysis.RESULTS -The frequency of the CTLA-4 G allele differed significantly between the type 1 diabetic patients (61%) and the normal control subjects (48%) (P = 0.016). The difference in the CTLA-4 G allele became greater between patients with a younger age of onset of type 1 diabetes (age at onset Ͻ30 years) and the normal control subjects (64% and 48%, respectively). However, the frequency of the CTLA-4 G allele did not differ between type 1 diabetic patients with younger and older age of onset (64% vs. 57%). The G allele frequencies in the patients with younger-onset type 1 diabetes and AITD increased more than in the control patients (P = 0.025). These differences reflected a significant increase in the frequency of G/G genotype-that is, 54% in those with younger-onset type 1 diabetes and AITD, 39% in those without AITD, and 28% in control subjects.CONCLUSIONS -An association was detected between the CTLA-4 gene polymorphism and younger-onset type 1 diabetes with AITD. The G variant was suggested to be genetically linked to AITD-associated type 1 diabetes of younger onset in this Japanese population. The defect in these patients presumably lies in a T-cell-mediated autoimmune mechanism. E p i d e m i o l o g y / H e a l t h S e r v i c e s / P s y c h o s o c i a l R e s e a r c h 976DIABETES CARE, VOLUME 23, NUMBER 7, JULY 2000 CTLA-4 gene A/G polymorphism in type 1 diabetes and AITDtide level of Ͻ20 µg/day (20). Blood was sampled at intervals of 6-12 months for the measurement of the thyroid autoantibodies (anti-thyroid peroxidase [TPO] and anti-thyroglobulin [TG] antibodies), GAD65 antibody, and IA-2 antibody. Antibodies were determined by radioimmunoassay (20,21). Cutoff levels of GAD65 antibody, IA-2 antibody, and thyroid autoantibody were 1.2, 0.5, and 0.4 U/ml, respectively. Thyroid autoantibodies were measured Ͼ3 times in all patients with diabetes during the follow-up period. When the thyroid autoantibodies were detected Ͼ2 times in same patient, autoantibodies were considered to be positive. The diagnosis of AITD was based on the finding of palpable goiter or the presence of chronic thyroiditis with ultrasonography examination in the...

Association of CTLA-4 Polymorphisms with Type 1 Diabetes in the Egyptian Population

“…Apart from re-sequencing, association of CTLA-4 variants in different populations is a strategy for further fine mapping. In general, the compelling data on the association of CTLA-4 polymorphisms with T1D is convincing in some populations including Belgian [4,9], French, Italian, Korean, Mexican, Spanish-American [10], Japanese [11][12][13][14][15], Chinese [16], Russian [17], British [18], Moroccan [19], Estonian [20], and Croatian [21] populations.…”

A type 1 diabetes subgroup with a female bias is characterised by failure in tolerance to thyroid peroxidase at an early age and a strong association with the cytotoxic T-lymphocyte-associated antigen-4 gene

“…However, the reported differences were not statistically significant. In three other studies, CTLA4 was reported to be associated with co-occurrence of type 1 diabetes and AITD [5,17,18], which is a form of autoimmune polyendocrine syndrome (APS) [2,19].…”

Association of Ctla-4 and PTPN-22 Genes Polymorphisms With Increased Risk of Autoimmune Thyroiditis in Tatar Population

“…Геномную ДНК из лейкоцитов венозной кро-ви выделяли методом фенол-хлороформной экс-тракции с некоторыми модификациями [14].…”

“…Однако подобные исследования, про-веденные для популяции коренных американцев и японцев, не показали очевидного сцепления данного локуса с риском развития АИТ у жен-щин молодого возраста. Это, возможно, является отражением влияния факторов окружающей сре-ды на реализацию мутаций в генах-кандидатах и фенотипическое проявление заболевания [14].…”